Streptozotocin- pancreatic damage in the rat: modulatory effect of 15-deoxy delta12,14-Prostaglandin J2 on nitridergic and prostanoid pathway

GONZÁLEZ ELIDA; JAWERBAUM ALICIA; SINNER DÉBORA; PUSTOVRH CAROLINA; WHITE VERÓNICA; CAPOBIANCO EVANGELINA; XAUS CARMEN; PERALTA CARMEN; ROSELLÓ-CATAFAU, JOAN

NITRIC OXIDE-BIOLOGY AND CHEMISTRY

ACADEMIC PRESS

Lugar: USA; Año: 2002 vol. 6 p. 214 - 220

1089-8603

15-deoxy-delta 12,14prostaglandin J2 (15d-PGJ2) has been identified as a natural ligand of the PPARgamma subtype. PPAR activation in non adipose tissues seems toinhibit iNOS and COX2 expression. Vasoactive compounds like nitric oxide and prostaglandins are increased in pancreatic tissue from streptozotocin diabeticrats. We hypothesize that 15d-PGJ2 may regulate the production of these proinflammatory compounds that lead to beta cell destruction in the diabeticpathology. In this work we evaluated Ca++-dependent (cNOS) and Ca++-independent (iNOS) activity, nitrate/nitrite levels, 15-dPGJ2 and prostaglandin E2 (PGE2) levels in isolated pancreatic islets, and 15d-PGJ2 levels in plasma from control and streptozotocindiabetic rats. Our results show that cNOS is predominant in control, while iNOS isoform is increased in thediabetic islets (P < 0.01). 15d-PGJ2 10-5M inhibitscNOS and iNOS activity both in control and diabetic islets (P < 0.05). Nitrate/nitrite and PGE2 levels are higher in diabetic than in control islets (P < 0.05 and P < 0.01, respectively). 15d-PGJ2 10-5M decreases nitrate/nitrite and PGE2 levels both in control and in diabetic islets. Bisphenol A diglycidyl ether (BADGE), a recently described PPAR antagonist, seems to act as a PPARgamma agonist, diminishing nitrate/nitrite and PGE2 levels in control and diabetic islets. 15d-PGJ2 production is lower in islets from diabetic animals compared to control (P < 0.05). Our observations suggest that 15d-PGJ2 is able to diminish the production of vasoactive proinflammatory agents in pancreatic islets. The diminished 15d-PGJ2 levels in the diabetic islets are probably related to the diminished capacity to limit the inflammatory response due to experimental diabetes in the rat.